1 AD pathology is more likely to be clinically 20% more women than - PowerPoint PPT Presentation

Disclosures Disclosures Objectives Objectives Sex Differences in Alzheimer’s Disease 1. Describe sex differences in the prevalence and 1. Describe sex differences in the prevalence and travel support from Abbott � incidence of Alzheimer’s Disease incidence of Alzheimer’s Disease Pauline M. Maki, Ph.D. Pauline M. Maki, Ph.D. consultant for Pfizer, Bayer, & Noven � 2. Understand how reproductive aging and hormone 2. Understand how reproductive aging and hormone Professor of Psychiatry and Psychology Professor of Psychiatry and Psychology therapy might influence the risk for AD therapy might influence the risk for AD therapy might influence the risk for AD therapy might influence the risk for AD University of Illinois at Chicago University of Illinois at Chicago � Research funding from NIH R h f di f NIH #MH083782, #HD055892, #AI082151, 3. Describe sex differences in risk factors for AD. 3. Describe sex differences in risk factors for AD. and #AI034993. Age- Age -adjusted death rates for selected leading causes adjusted death rates for selected leading causes Sex differences in top 10 causes of death in Sex differences in top 10 causes of death in Objectives Objectives of death: United States, 1958 of death: United States, 1958- -2005 2005 the U.S. the U.S. ICD-7 ICD-8 ICD-9 ICD-10 2.5 1,000.0 1. Describe sex differences in the prevalence and 1. Describe sex differences in the prevalence and Heart disease Heart disease 1 incidence of Alzheimer’s Disease incidence of Alzheimer’s Disease 2 Malignant neoplasms Malignant neoplasms U.S. standard Cerebrovascular 2 3 diseases 100.0 Cerebrovascular diseases 2. Understand how reproductive aging and hormone 2. Understand how reproductive aging and hormone Accidents 5 Chronic lower respiratory therapy might influence the risk for AD therapy might influence the risk for AD therapy might influence the risk for AD therapy might influence the risk for AD ion diseases 1.5 1.5 Nephritis, nephrotic p , p Rate per 100,000 U populat 9 syndrome and nephrosis Accidents 10.0 3. Describe sex differences in risk factors for AD. 3. Describe sex differences in risk factors for AD. Hypertension Diabetes mellitus 13 1 14 Alzheimer's disease Parkinson’s disease 1.0 Influenza and pneumonia 7 Alzheimer’s 0.5 disease Nephritis, nephrotic syndrome and nephrosis 0.1 Septicemia 1958 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 0 Male: Female Ratio 1 Circled numbers indicate ranking of conditions as leading causes of death in 2005. Source: CDC National Vital Statistics Report, Kung et al. Deaths: Final Data for 2005; Vol 56, No 10, 2008 Source: CDC National Vital Statistics Report, Source: CDC National Vital Statistics Report, Kung et al. Deaths: Final Data for 2005; Vol 56, No 10, 2008 Source: CDC National Vital Statistics Report, Source: CDC National Vital Statistics Report, Source: CDC National Vital Statistics Report, Kung et al. Deaths: Final Data for 2005; Vol 56, No 10, 2008 Source: CDC National Vital Statistics Report, Kung et al. Deaths: Final Data for 2005; Vol 56, No 10, 2008 Source: CDC National Vital Statistics Report, 1

AD pathology is more likely to be clinically 20% more women than men die of Alzheimer’s 20% more women than men die of Alzheimer’s EURODEM: A 65- EURODEM: A 65 -year year- -old woman has a greater old woman has a greater expressed as dementia in women even after adjusting for age (longevity) even after adjusting for age (longevity) risk of AD compared to a man risk of AD compared to a man per 100,000 Women Men Mortality Rate Andersen, K et al. Gender differences in the incidence of AD and vascular dementia: The EURODEM Studies. Andersen, K et al. Gender differences in the incidence of AD and vascular dementia: The EURODEM Studies. Moschetti Moschetti et al., 1999 et al., 1999- -2008. 2008. JAGS JAGS 2012 Aug;60(8):1509 2012 Aug;60(8):1509- -14. Burden of Alzheimer's disease 14. Burden of Alzheimer's disease- -related mortality in the related mortality in the Barnes, L et al. Sex Differences in the Clinical Manifestations of Alzheimer Disease Pathology. Barnes, L et al. . United States United States Neurology Neurology . 53(9):1992 . 53(9):1992- -1997, December 10, 1999. 1997, December 10, 1999. Arch Gen Psychiatry. 2005;62(6):685-691. . . Greater cognitive deterioration in women than Paradoxically, risk of MCI is higher in men AD/MCI Paradox men with Alzheimer's: A meta analysis Male Advantage Female Advantage Cognitive Domain � Rate of MCI higher in men, but rate of AD Semantic higher in women. Nonsemantic � Women might transition from normal cognition directly to dementia at a later cognition directly to dementia at a later Verbal Verbal age but might transition more abruptly. Visuospatial Memory -1.0 -0.75 -0.50 -0.25 0 0.25 0.50 0.75 Effect Size (95% CI) Note. A negative effect size (Hedges’s d ) denotes a male advantage and a positive effect size a female advantage. Petersen, RC et al. The incidence of MCI differs by subtype and is higher in men: the Mayo Clinic Study of Aging. Petersen, RC et al. Petersen, RC et al. Petersen, RC et al. The incidence of MCI differs by subtype and is higher in men: the Mayo Clinic Study of Aging. Adapted from Irvine, et al. Greater cognitive deterioration in women than men with Alzheimer's disease: A meta analysis Adapted from Irvine, et al. Neurology. 2012 Jan 31;78(5):342-51. Neurology. 2012 Jan 31;78(5):342-51. JCEN . 2012; . 2012; 2012;34(9):989-98 . . JCEN 2

Uncertainty about hormone therapy and Uncertainty about hormone therapy and Objectives Objectives Women- Women -specific risk factors for AD specific risk factors for AD risk for AD risk for AD � Menopause and menopausal symptoms � Menopause and menopausal symptoms 1. Describe sex differences in the prevalence and 1. Describe sex differences in the prevalence and � Hysterectomy and oopherectomy (removal of uterus � Hysterectomy and oopherectomy (removal of uterus � Risk factor for AD? � Risk factor for AD? incidence of Alzheimer’s Disease incidence of Alzheimer’s Disease and ovaries) and ovaries) � Protective against AD? � Protective against AD? � Use of hormone therapy � Use of hormone therapy 2. Understand how reproductive aging and hormone 2. Understand how reproductive aging and hormone � Neutral? � Neutral? therapy might influence the risk for AD therapy might influence the risk for AD therapy might influence the risk for AD therapy might influence the risk for AD � Other hormone treatments � Other hormone treatments � Other hormone treatments � Other hormone treatments � Osteoporosis � Osteoporosis � Depends on conditions – age, health? � Depends on conditions – age, health? 3. Describe sex differences in risk factors for AD. 3. Describe sex differences in risk factors for AD. � Breast cancer � Breast cancer Observational Studies Show a Decreased Risk Observational Studies Show a Decreased Risk Women’s Health Initiative Memory Study Women’s Health Initiative Memory Study Critical Window Hypothesis Critical Window Hypothesis of AD in Hormone Therapy Users of AD in Hormone Therapy Users CEE Alone Placebo Heyman et al, 1984 (n = 1464) (n = 1483) HR (95% CI) � The neuroprotective effects of hormone therapy � The neuroprotective effects of hormone therapy Amaducci et al, 1986 depend on timing of initiation in relation to the depend on timing of initiation in relation to the Broe et al, 1990 Cases of probable dementia † 28 19 1.49 (0.83–2.66) Graves et al, 1990 menopause and/or age menopause and/or age Brenner et al, 1994 Rate per 10,000 person-years 37 25 Henderson et al, 1994 Mortel & Meyer, 1995 � Initiation of hormone therapy early in the � Initiation of hormone therapy early in the Retrospective † Mean follow-up in CEE alone vs placebo arms: 5.21 ± 1.73 years. Shumaker SA, et al. JAMA . 2004;291:2947-58. Paganini-Hill & Henderson, 1996 Prospective Prospective menopausal transition is associated with menopausal transition is associated with Baldereschi et al, 1998 Waring et al, 1999 Meta-Analysis CEE+MPA Placebo cognitive benefit but later initiation confers no cognitive benefit but later initiation confers no Slooter et al, 1999 (n = 2229) (n = 2303) HR (95% CI) Seshadri et al, 2001 cognitive benefit cognitive benefit Tang et al, 1996 Cases of probable dementia* 40 21 2.05 (1.21–3.48) Kawas et al, 1997 Zandi et al, 2002 Rate per 10,000 person-years 45 22 Shumaker SA, et al. 2003 * * Yaffe et al, 1998 Hogervorst et al, 2000 LeBlanc et al, 2001 *Mean follow-up in CEE+MPA vs placebo arms: 4.05 ± 1.19 years. Shumaker SA, et al. JAMA . 2003;289:2651-62. 0 1 2 3 4 *Confidence interval not provided. Relative Risk (95% CI) Adapted from LeBlanc ES, et al. JAMA . 2001;285:1489-1499. 3